Autocrine growth stimulation by transforming growth factor-α in human non-small cell lung cancer

E. A. Putnam, N. Yen, G. E. Gallick, P. A. Steck, K. Fang, B. Akpakip, A. F. Gazdar, J. A. Roth

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39 Citations (Scopus)

Abstract

We studied the biological response to and production of transforming growth factoralpha (TGF-α) by the non-small cell lung carcinoma (NSCLC) clonal cell lines H226b, H322a, H460a, H596b. Each of these cell lines expressed epidermal growth factor receptor (EGFR) as determined by [125I]EGF competitive binding and Scatchard analysis and by phosphorylation. The receptors were functionally active as determined in immune complex kinase assays. H322a, H226b, H460a, and H596b cells showed stimulated [3H]thymidine (Thd) uptake in response to TGF-α. Exogenously added TGF-α increased colony formation in soft agar for three of the cell lines in media containing serum. All cell lines expressed TGF-α detected by immunohistochemistry and TGF-α mRNA, although to differing degrees. Cell lysates and spent media competed for EGFR binding with EGF, thus demonstrating production of TGF-α-like activity. The anti-TGF-α monoclonal antibody AB-3 inhibited the uptake of [3H]Thd by proliferating H322a and H226b cells but not H460a and H596b cells. No inhibition occurred with MOPC21 antibody and inhibition was completely reversed by addition of TGF-α to the culture. Suramin inhibited cell proliferation and [3H]Thd uptake by all cell lines. Inhibition of H460a and H596b cells was reversed with exogenous TGF-α but not PDGF. Our data suggests that TGF-α is a mediator of autocrine growth stimulation for NSCLC cells, and that for some NSCLC cells cytoplasmic binding of receptor and ligand is the primary mechanism for autocrine growth stimulation.

Original languageEnglish
Pages (from-to)49-60
Number of pages12
JournalSurgical Oncology
Volume1
Issue number1
DOIs
Publication statusPublished - 1992 Feb

Keywords

  • autocrine
  • epidermal growth factor receptor
  • lung cancer
  • transforming growth factor alpha

ASJC Scopus subject areas

  • Surgery
  • Oncology

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  • Cite this

    Putnam, E. A., Yen, N., Gallick, G. E., Steck, P. A., Fang, K., Akpakip, B., Gazdar, A. F., & Roth, J. A. (1992). Autocrine growth stimulation by transforming growth factor-α in human non-small cell lung cancer. Surgical Oncology, 1(1), 49-60. https://doi.org/10.1016/0960-7404(92)90056-Q